Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas

Abstract

The effectiveness of pharmacological therapy for the treatment of wounds is variable, as well as its side effects, which drives the search for new therapeutic modalities, among them products based on medicinal plants and nanotechnology. Chrysin, a flavonoid found in several plant species, has pharmacological properties such as: antioxidants, anti-inflammatories, antimicrobials, antibacterials and antiallergic agents that can contribute to an adequate scar repair. In this way, the work aimed to evaluate the effects of bioactive collagen membranes containing chrysin in liposomes on the healing of skin wounds in an animal model of excisional skin wounds. 72 rats (Wistar) and 18 male mice (Swiss) were used, submitted to a cutaneous excision and randomized in the groups according to treatment: without intervention - (SI); control - collagen membrane containing liposomes (COL) and collagen membrane containing chrysin in liposomes (COL / CRI) - patent filed with INPI BR 10 2019 018341 1. The experimental protocols were approved by CEPA / UFS (55/2018). Wound areas were measured using an 8 mm diameter digital caliper on the 3rd, 7th, 14th and 21st day postinjury and histologically evaluated (hematoxylin-eosin stain) for response and type of inflammatory infiltrate, granulation tissue, proliferation fibroblasts, deposition of collagen fibers and re-epithelialization in the healing area. The effect of membranes containing chrysin was evaluated for vascular endothelial growth factor (VEGF) and kappa nuclear factor B (NFkB) by Western blot, interleukins IL-1β and IL-6 by ELISA and SOD and CAT by the colorimetric method. Differences between groups were analyzed using the one-way ANOVA test, followed by the Tukey post-test. The results were expressed as mean ± E.P.M. and considered significant when p <0.05. The chrysin content in the membranes was 165.37 ± 11.70 μg · cm-2, obtaining an encapsulation efficiency of 87.82%. In the analysis of the wound reduction area, the animals treated with COL / CRI significantly increased the percentage of wound reduction on the 3rd day when compared to the SI group (p <0.05) and on the 7th day when compared to the SI groups (p <0.001) and COL (p <0.01). In assessing the intensity of the inflammatory reaction, COL / CRI decreased the inflammatory profile on the 3rd and 7th day when compared to the SI (p <0.001) and COL (p <0.01) groups, respectively. In histomorphological analysis, COL / CRI significantly increased the rates of epithelialization of residual wounds on the 3rd day when compared to the SI (p <0.001) and COL (p <0.05) groups and on the 7th day when compared to the SI groups (p <0.001) and COL (p <0.01). In the assessment of inflammatory activity on the 7th post-injury day, the COL / CRI group significantly decreased NFkB levels when compared to the SI group (p <0.05) and the levels of interleukins IL-1β and IL-6 ( p <0.001) when compared to the SI group (p <0.001). On the 7th post-injury day, COL / CRI significantly increased VEGF levels when compared to the SI (p <0.01) and COL (p <0.001) group. In the antioxidant evaluation on the 7th day after injury, COL / CRI significantly increased SOD levels when compared to the SI group (p <0.05) and CAT when compared to the SI group (p <0.001). It is concluded, therefore, that the membranes containing chrysin have antioxidant, anti-inflammatory, angiogenic and healing actions representing a promising biotechnological alternative with clinical application for the treatment of wounds.